Gene therapy for ocular diseases

Abstract

The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

Reprogramming of adult rod photoreceptors prevents retinal degeneration

“…Many research groups have focused on targeted gene therapy as a treatment for this disease (2,3). However, retinal disease can be caused by mutations in any one of more than 200 genes (4), and the pathogenic mechanisms of various mutations differ greatly (5).…”

Modulation of Transgene Expression in Retinal Gene Therapy by Selective Laser Treatment

“…4 Additional programs are advancing toward the clinic or are in ongoing clinical trials, including the treatment of age-related macular degeneration (AMD), 5,6 retinitis pigmentosa, retinoschisis, and Stargardt's disease. 7 Gene therapy for retinal neovascular diseases, which affect a large and growing population, are of specific interest because of the high prevalence of these diseases and the high burden of care under current therapeutic regimens. AMD is the leading cause of visual loss in patients > 50 years old, with 7.5 million people likely to be affected by AMD-related visual impairment in the United States by 2020.…”

Surgical treatment for complications of congenital retinoschisis

“…And progress in the genetic therapy for congenital retinoschisis due to the continuous efforts of scholars is encouraging [26][27][28][29][30] , which holds considerable promise for the future management of this disease.…”